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Echocardiographic Imaging for TranscatheterAortic Valve Replacement

Rebecca T. Hahn, MD, Alina Nicoara, MD, Samir Kapadia, MD, Lars Svensson, MD, PhD,and Randolph Martin, MD,

New York, New York; Durham, North Carolina; Cleveland, Ohio; and Atlanta, Georgia

Transcatheter aortic valve replacement has become an accepted alternative to surgery for patients with se-vere, symptomatic aortic stenosis who are inoperable or are at high surgical risk. Recent trials support theuse of transcatheter aortic valve replacement also in patients at intermediate risk, and ongoing trials are as-sessing appropriateness in other patient groups. The authors review the key anatomic features integral tothe transcatheter aortic valve replacement procedure and the echocardiographic imaging required for prepro-cedural, intraprocedural, and postprocedural assessment. (J Am Soc Echocardiogr 2017;-:---.)

Keywords: Aortic stenosis, Transcatheter aortic valve replacement, Echocardiography

Transcatheter aortic valve replacement (TAVR) is now a class Irecommendation for treatment of prohibitive-risk and high–surgi-cal risk patients with severe, symptomatic aortic stenosis (AS).1

TAVR currently has a class IIa recommendation for patients at in-termediate surgical risk, but given the large randomized trialsshowing noninferiority to surgical aortic valve replacement,TAVR may be an appropriate alternative in this population aswell.2,3 TAVR volumes continue to increase as indications foruse expand.4,5 In this article, we review the anatomic featuresintegral to the TAVR procedure and the echocardiographicimaging required for preprocedural, intraprocedural, andpostprocedural assessment.

ANATOMIC PERSPECTIVE

Characterization of the aortic root complex, consisting of theaortic valve, aortic annulus, sinuses of Valsalva, and sinotubularjunction, is critical for planning and success of TAVR. The normalaortic valve has three leaflets supported by the aortic sinuses: left,right, and noncoronary. The right coronary leaflet rests on themuscular part of the interventricular septum, the noncoronaryleaflet is adjacent to the membranous septum and the anteriormitral leaflet, and the left coronary leaflet is continuous with theanterior mitral leaflet (aortomitral curtain) and muscular interven-

ia University Medical Center, New York, New York (R.T.H.); Duke

dical Center, Durham, North Carolina (A.N.); Cleveland Clinic,

io (S.K., L.S.); and Emory University, Atlanta, Georgia (R.M.).

terest: Dr. Hahn is the Cardiovascular Research Foundation echo-

core laboratory director for a number of trials, including the PART-

which she receives no direct compensation.

sts: Rebecca T. Hahn, MD, Columbia University Medical Center,

esbyterian Hospital, 177 Fort Washington Avenue, New York,

ail: [email protected]).

6.00

7 by the American Society of Echocardiography.

/10.1016/j.echo.2017.10.022

tricular septum (Figure 1).6 Between the semilunar hinge lines ofthe leaflets are the fibrous interleaflet trigones or triangles.7 Theanatomic aortic annulus is defined as the semilunar lines of attach-ment of the aortic valve leaflets to the aortic sinuses. However,measurement of the aortic annulus relevant to transcatheter heartvalve (THV) sizing is performed at the most ventricular (basal)hinge points of the leaflets, referred to as the ventricular ring.More than half the circumference of this ring is formed by thebase of the interleaflet triangles; this plane is thus the ‘‘virtual’’annulus. The coronary arteries arise at a variable distance fromthe base of left and right coronary cusps.8 The left coronary ostiumis frequently in the posterior part of the left sinus, and the rightcoronary ostium is somewhat anterior and superior in the right si-nus. The lower position of the left coronary increase its risk forobstruction by a calcified aortic leaflet.9 Also, the atrioventricularbundle then courses on the top of the muscular septum underthe membranous septum, where it divides into the left and rightbundles (Figure 1) and thus is at risk for damage with TAVR de-pending in part on the depth of THV implantation.10,11 Theatrioventricular bundle then courses on the top of the muscularseptum under the membranous septum.

One important anatomic variation is the bicuspid aortic valve,which was an exclusion criterion for early TAVR trials12,13 and maybe associated with worse procedural outcomes compared withtrileaflet valves.14,15 Anatomic differences compared with thetrileaflet valve include a larger and more circular annulus, largersinus of Valsalva and ascending aorta, and more eccentric annularcalcification,16 which may contribute to greater degrees of post-TAVR paravalvular aortic regurgitation (PAR)15,17 and a higherincidence of post-TAVR conduction abnormalities.18 The BicuspidTAVR Registry has recently shown good success rates in these patientsusing new-generation transcatheter valves.19 Improved preproceduralsizing using multislice computed tomography (MSCT)15 as well as im-plantation techniques may mitigate these complications. Bicuspidvalves were classified by Sievers and Schmidtke20 as type 0, no raphe;type 1, with one raphe (most commonly seen between the left andright coronary cusps); and type 2, with two raphes. Type 1 bicuspidaortic valve anatomy with left and right cusp fusion may have betterpost-TAVR outcomes compared with other anatomic variants.21

1

Delta:1_given name

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mailto:[email protected]

https://doi.org/10.1016/j.echo.2017.10.022

Figure 1 Conduction system. The aortic valve node is typicallylocated on the floor of the right atrium just posterior (post) andinferior to the membranous septum (blue shaded region). Theatrioventricular (A-V) node and bundle then courses on the topof the muscular septum under the membranous septum, whereit divides into the left and right bundles. ant, Anterior; IVS, inter-ventricular septum; LM, left main coronary artery; RCA, rightcoronary artery.

Abbreviations

2D = Two-dimensional

3D = Three-dimensional

ACC = American College of

Cardiology

AHA = American Heart

Association

AS = Aortic stenosis

AVA = Aortic valve area

BSA = Body surface area

CS = Conscious sedation

EF = Ejection fraction

ELI = Energy loss index

GA = General anesthesia

GLS = Global longitudinal

strain

HR = Hazard ratio

LV = Left ventricular

LVOT = Left ventricular

outflow tract

MR = Mitral regurgitation

MSCT = Multislice computed

tomography

PAR = Paravalvular aortic

regurgitation

PARTNER = Placement of

Aortic Transcatheter Valves

TAVR = Transcatheter aortic

valve replacement

TEE = Transesophageal

echocardiography

THV = Transcatheter heartvalve

TR = Tricuspid regurgitation

TTE = Transthoracicechocardiography

VARC = Valve AcademicResearch Consortium

Zva = Valvuloarterialimpedance

2 Hahn et al Journal of the American Society of Echocardiography- 2017

PREPROCEDURAL

IMAGING WITH

ECHOCARDIOGRAPHY

The current American HeartAssociation (AHA)/AmericanCollege of Cardiology (ACC)and European Association ofCardiovascular Imaging valvularheart disease guidelines1,22

discuss the importance of theheart team approach to themanagement of complex valvularheart disease. An important partof that team is the cardiovascularimaging specialist. Throughoutthe development of the TAVRprocedure for severe, symptomaticAS, echocardiographic imaginghas played an essential role inthe preprocedural assessment ofpatients, intraprocedural guidance,and postprocedural follow-up.23,24 As indications for bothsurgical aortic valve replacementand TAVR continue to evolve,1

echocardiography may play aneven more important role in pa-tient diagnosis and management.In this section we review the roleof echocardiography in the selec-tion of patients for TAVR.

Morphology of the AorticValve

Distinguishing bicuspid fromtricuspid aortic valve is essentialbefore TAVR. Although multi-ple imaging modalities canassess the morphology of theaortic valve and root, the diag-nosis of bicuspid aortic valve istypically made using echocardi-ography. The short-axis viewsof the valve in systole shouldimage a typical ‘‘fish-mouth’’appearance of valve openingand absence of opening at theraphe. Systolic doming fromthe long-axis view may beanother clue of a bicuspid valve.

In patients with good-quality transthoracic images who do not havedense calcification, diagnostic sensitivity and specificity for identifi-cation of a bicuspid valve are >70% and >90%, respectively,25,26

but diagnostic uncertainty may remain in 10% to 15% of patientsafter echocardiography.27 In the setting of calcification withreduced leaflet excursion in systole, the abnormal motion of thetwo cusps may not be appreciated, and color Doppler may behelpful in distinguishing immobile trileaflet aortic valves withoutcommissural fusion from bicuspid valves with fusion; color

Doppler flow in all three commissures should be seen with trileafletvalves.28

In addition to determining the number of cusps, the locationand severity of calcium are important aspects of morphologicassessment. The prognostic importance of valve calcium by echo-cardiography has long been recognized,29,30 but MSCT hasbecome the primary imaging modality for quantification ofcalcium burden.31-33 Ectopic calcification of the left ventricularoutflow tract (LVOT) is predictive of PAR.34,35 In addition, inpatients with low flow, the severity of calcification may helpdistinguish those patients with true severe AS from thosepatients with pseudosevere AS.36-38 Sex-specific criteria havebeen established, with aortic valve calcium cutoffs for severe ASof $1,275 arbitrary units in women and 2,065 arbitrary units inmen. Interestingly, aortic valve calcium is also lower in womenafter indexing to body size or annular area,37,39 consistent withfindings of increased fibrosis in women.40

Assessment of Severity of AS

Echocardiography is used to assess valve morphology and severityof stenosis, as well as the cardiac response to AS, including left ven-tricular (LV) remodeling and function, mitral valve regurgitation, andpulmonary hypertension. Recent updates to the American Societyof Echocardiography and European Society of Echocardiographyguidelines,41 as well as an associated letter to the editor,42 reviewthe echocardiographic parameters and acquisition recommenda-tions. These parameters can be divided into flow-dependentmeasurements and flow-independent measurements and are sum-marized in Table 1.

The greatest error in the aortic valve area (AVA) calculation is thesquared LVOT diameter measurement. There are important caveatsabout the measurement of the LVOT diameter in the setting of AS(Figure 2, Table 2).

Table 1 Standard echocardiographic parameters used to assess the severity of AS

Mild Moderate Severe

Valve anatomy

� Mild leaflet calcification or

thickening with reduction insystolic motion

� Mild to moderate leaflet

calcification of a bicuspid ortrileaflet valve with some

reduction in systolic motion or

� Rheumatic valve changes with

commissural fusion

� Severe leaflet calcification or

congenital stenosis withseverely reduced leaflet

opening

Quantitative parameters (flow dependent)

Peak velocity (m/sec) 2.0–2.9 3–3.9 $4

Mean gradient (mm Hg) <20 20–39 $40

Quantitative parameters (flow independent)

Doppler index >0.5 0.26–0.5 #0.25

AVA (cm2) >1.5 1.1–1.5 #1.0

AVA index (cm2/m2)* >0.85 0.61–0.85 #0.6

*Indexing valve area is particularly important in smaller patients with height < 135 cm (65 in), BSA < 1.5 m2, or body mass index < 22 kg/m2.

Figure 2 Transthoracic and transesophageal echocardiographic optimization of LVOTmeasurement. Simultaneous biplane imagingfrom transthoracic (A,B) as well as transesophageal (C,D) imaging shows that an appropriately centered aortic valve in the long-axisview (A or C) will image the right coronary cusp (RCC) hinge point anteriorly (B or D) and the interleaflet trigone (between the left cor-onary cusp [LCC] and noncoronary cusp [NCC]) posteriorly. The maximum sagittal plane LVOT diameter (yellow arrow) should bemeasured from the inner edge to inner edge of the RCC hinge point/septal border to the posterior trigone/anterior mitral leaflet border.Importantly, the LVOT diameter measurement should avoid including ectopic calcium on the anterior mitral valve leaflet.

Journal of the American Society of EchocardiographyVolume - Number -

Hahn et al 3

Table 2 Summary of measurement pitfalls and recommended techniques for accurate quantitation of AVA

Pitfall Incorrect example Correct measurement Correct example

Particularly in the setting of upper

septal hypertrophy, there is

progressive narrowing of the

LVOT within the left ventricle;measuring the LVOT diameter

5–10 mm below the annulus will

result in significantunderestimation of the AVA by

continuity equation (CE)

Measure the LVOT diameter

at the level of the aortic

annulus

Ectopic calcium frequently is seen

within the LVOT, on the LV sideof the A2 mitral valve scallop is

not circumferential, thus

measuring inside this calcium

ridge will result in significantunderestimation of the AVA by

CE

Exclude ectopic calcification in

the LVOT or annulus whenmeasuring the annulus

Flow acceleration is seen proximal

to a region of stenosis; placingthe pulsed-wave sample

volume at the annulus (red) will

result in overestimation of theAVA by CE

At level of red sample volume Position the pulsed-wave sample

volume in a region just proximalto the flow acceleration such

that the spectral Doppler profile

shows no opening or closureclicks

At level of green sample volume

The appropriate pulsed-wave

spectral profile should

represent laminar flow (nospectral broadening) and trace

the modal velocity (most

frequently sampled velocity in

the spectral profile, not themaximum velocity of a few red

blood cells); tracing the faint

spectral will overestimate

stroke volume and AVA

Reducing the gain or increasing

the reject will result in a spectral

profile showing the modalvelocity; the black-white

interface should then be traced

(Continued )


Table 2 (Continued )

Pitfall Incorrect example Correct measurement Correct example

Off-axis imaging of the vena

contracta (narrowest, highest

velocity portion of the jet) willlead to underestimation of the

severity of stenosis; seeing a

‘‘double envelope’’ of dense

LVOT flow (blue trace), andfainter transaortic flow (red

trace) may indicate that the

insonation beam is angled awayfrom the vena contracta

Adjust the imaging window to find

the densest, most uniform

continuous-wave spectralprofile

The direction of the transaortic jetmay often be anterior and to the

right; assuming the peak

velocity from a single apicalwindow will underestimate the

severity of stenosis in up to 50%

of patients

The right parasternal window inthis patient showed peak

velocities that were 0.5 m/sec

higher; amultiwindow approachis always recommended


Hahn et al 5

� LVOT diameter should be measured at early to mid-systole (when the ellip-tical LVOT is more circular) from the image that provides the largest diam-eter.43

� LVOT diameter should bemeasured from the inner edge to inner edge fromwhere the anterior (right coronary) cusp meets the ventricular anterosep-tum, to the posterior ‘‘virtual annulus’’ where the posterior interleaflet trian-gle meets the anterior mitral leaflet.44 Avoid measuring the ectopic calciumas a border of the LVOT.

� LVOT diameter measured below the aortic annulus underestimatescatheter-derived AVA.43,45 This may be particularly true in the setting of asigmoid septum.

� AVA calculated with LVOT diameter measured at the level of the aorticannulus is more accurate and reproducible.45-47

� Because the greatest error in AVA calculation is the squared LVOT diametermeasurement, using the ratio of VLVOT/VAS jet or VTILVOT/VTIaortic valve canbe a good indicator of AVA. A Doppler velocity index of #0.25 indicatessevere stenosis.

Although echocardiographic guidelines recommend a singlediameter measurement of the LVOT to calculate AVA, planimetryof the aortic valve and LVOT area by real-time three-dimensional(3D) methods has been shown to be accurate and reproduc-ible48,49 and to compare favorably with MSCT.50,51 Somestudies suggest that using a direct area measurement of theLVOT in the continuity equation may yield a more accuratemeasurement of AVA.52,53 However, Clavel et al.54 comparedthe two methods for calculating AVA: the hybrid multislicecomputed tomographic planimetered LVOT in the continuityequation and the standard echocardiographic continuity equation.Compared with echocardiographic AVA, the hybrid method didnot improve the correlation with transvalvular gradient, concor-dance between gradient and AVA, or prediction of mortality.

Importantly, thresholds for excess mortality differed between tech-niques: AVA # 1.0 cm2 for the echocardiographic method versus#1.2 cm2 for the hybrid method. These findings and other out-comes studies using the echocardiographic method for calculatingAVA54,55 support the continued use of standard linear LVOTdimension to measure AVA and to guide management asrecommended by current guidelines.1

Because small-sized patients may not require the same amount ofcardiac output as larger patients, the American Society ofEchocardiography recommends indexing the valve area to body sur-face area (BSA), particularly in smaller patients with height < 135 cm(65 in), BSA < 1.5 m2, or body mass index < 22 kg/m2. The ACCguidelines use an indexed AVA of #0.6 cm2/m2 to define severeAS. Importantly, indexing to BSAmay not be appropriate in obese pa-tients.41

Some investigators have suggested that using an indexed cut-off of<0.5 cm2/m2 may not only reduce inconsistent measurements withunindexed values,47,56 but lower indexed AVA cut-offs may alsoimprove the prediction of outcomes.56,57

Low-Gradient, Severe AS

As many as 40% of patients with AS may have discordant Dopplerhemodynamics with low mean gradient (<40 mm Hg) in the settingof severely reduced valve area (#1.0 cm2). Many of these patientshave low flow, currently defined as a stroke volume index of<35 mL/m2. Current AHA/ACC guidelines have subdivided the se-vere, symptomatic AS group of patients (stage D) into three separatecategories: high-gradient AS (stage D1); low-flow, low-gradient ASwith reduced ejection fraction (EF; stage D2); and low-gradient AS

Figure 3 Classification and characterization of the different types of AS according to AVA, gradient, LVEF, and flow. Classification oftypes of AS, including only the categories associated with symptoms and/or depressed LVEF. It does not include stage C1 (i.e., pa-tients with high-gradient AS, no symptoms, and preserved LVEF).Question mark indicates stage labels or indications for aortic valvereplacement (AVR) that are proposed but are not included in the guidelines and will need to be further tested and validated. AVAi,Indexed AVA; MG, mean gradient; RCT, randomized controlled trial; SVi, stroke volume index. Reproduced with permission fromClavel et al.58


with normal EF (stage D3). Figure 3 shows the suggested approach tothese subgroups of severe symptomatic AS.

Classic low-flow, low-gradient (mean gradient < 40 mm Hg) AS(AVA # 1 cm2) with reduced EF (<50%; stage D2 in the ACC/AHA guidelines) is often associated with coronary artery diseasebut may have intrinsic disease of the myocardium or afterloadmismatch related to severe stenosis. Because valve area has beenshown to be flow dependent,59,60 multiple studies have usedlow-dose dobutamine stress echocardiography to increase thetransvalvular flow rate while avoiding myocardial ischemia.61-65

The protocol for this test is described in the American Society ofEchocardiography updated guidelines.41

The D3 category of low-gradient, severe AS with normal EF is alsoknown as ‘‘paradoxical AS.’’ Because velocity and gradient are depen-dent on flow, a number of physiologic situations can result in low flowin the setting of normal EF: tachycardia,66 bradycardia,67 hyperten-sion,68-70 small ventricular cavity,71 severe diastolic dysfunction, se-vere mitral or tricuspid valve disease,72 pulmonary hypertension,and right ventricular dysfunction.73 The AHA/ACC guidelines donot advocate using dobutamine stress echocardiography with EF >50%. Recent studies on the use of quantitative valve calcium scoringby MSCT may be useful.36-38

If both flow and gradient are used to subcategorize patientswith severe AS, then four categories may be generated(Figure 3).58 The four different hemodynamic categories of pa-tients with AS on the basis of flow (normal, >200 mL/sec) andgradient (high, >40 mm Hg): normal flow and high gradient,normal flow and low gradient, low flow and high gradient, andlow flow and low gradient.74 The normal-flow, low-gradient entityis more difficult to explain, but this may be related to the use ofstroke volume to define ‘‘normal flow’’ (i.e., stroke volumeindex $ 35 mL/m2). Flow (in milliliters per second) is calculated

as stroke volume divided by ejection time. It is possible that pa-tients with normal flow and low gradient have normal stroke vol-ume in the setting of a prolonged ejection time, thus resulting in alow gradient.

Planimetry

Two-dimensional (2D) and 3D echocardiographic direct planimetryof the stenotic valve orifice can be also used to determine stenosisseverity.48,75-78 Using 2D transthoracic echocardiographicplanimetered AVA, Okura et al.75 showed that 2D transthoracic echo-cardiographic planimetry of AVA had a low standard error of esti-mates compared with valve area measured using transesophagealechocardiographic planimetry, the continuity equation, or theGorlin equation (0.04, 0.09, and 0.10 cm2, respectively).Importantly, planimetry and the Gorlin equation both measure theanatomic AVA, as the latter uses a correction coefficient for flowcontraction.79 This flow contraction leads to the formation of the‘‘vena contracta’’ beyond the anatomic orifice area. The area of thevena contracta represents the effective orifice area calculated by thecontinuity equation and is theoretically different from the areameasured by planimetry. Multiple studies have suggested that 3D pla-nimetered AVA may be more accurate, allowing alignment of the tipsof all leaflets in the short-axis view. These measurements may belarger than 2D measurements77,80 and show a lower meandifference with continuity equation calculations.77

Other Measures of AS Severity

Althoughmeasures of valve resistance, pressure recovery, energy loss,and arterial compliance and impedance are not recommended forroutine clinical use, somemay have significant prognostic informationin certain subgroups of patients.


Hahn et al 7

Differences in catheterization and echocardiographicallymeasured gradients can arise in the setting of downstream pressurerecovery.81-83 This net pressure drop between the left ventricle andthe ascending aorta is the pathophysiologically relevantmeasurement and more representative of the geometric valvearea. The energy loss index (ELI) is another measure that attemptsto account for the total fluid mechanical energy loss related toboth valve area and ascending aortic area.84 The ELI is calculatedas ELI = [effective orifice area � AA/AA � effective orifice area]/BSA. Similar to valve area, it is less flow dependent than gradientor peak velocity, takes into account pressure recovery, and isroughly equivalent to effective orifice area measured by catheteriza-tion.85 Using the ELI, a substudy of the Simvastatin and Ezetimibe inAortic Stenosis trial reclassified 47.5% of patients from severe tononsevere AS.86 The energy loss is most significant in small aortas(<30 mm). An ELI of #0.5 to 0.6 cm2/m2 is consistent with severeAS.86,87

Finally, an index of global LV hemodynamic load, valvuloarterialimpedance (Zva), accounts for both the load of the aortic valve andthe increase in vascular resistance. An increase in systemic vascularresistance may be a compensatory mechanism in the setting ofreduced transvalvular flow. Concomitant arterial hypertensionis found to be present in a large proportion (35%–51%) ofpatients with AS.88-90 Zva is calculated as Zva = systolic bloodpressure + DPmean/stroke volume index.88 Several investigatorshave shown that the risk for mortality was increased with an increasein Zva.

88,89,91-93 Hachicha et al.89 found an increase in mortality of2.76-fold in patients with Zva $ 4.5 mm Hg $ mL�1 $ m2 and by2.30-fold in those with Zva between 3.5 and 4.5 mm Hg $ mL�1 $m2 after adjusting for other risk factors.

Stress Testing in AS

The indications for stress testing for severe AS include determinationof the etiology of symptoms in the setting of nonsevere disease, confir-mation of asymptomatic status in the setting of severe disease, andevaluation of patients with concomitant valvular and myocardialdysfunction.94

Because of the poor prognosis associated with symptom onset,95

determination of symptom status is an important role for stress testingin patients reporting no symptoms with severe AS.22,96 A number ofparameters have been used to indicate a positive exercise treadmilltest in the setting of AS:

� development of symptoms (limiting breathlessness, chest pain or tightness,dizziness, and syncope);97,98

� development of arrhythmias (three consecutive ventricular premature beatsor other complex ventricular arrhythmias);97,98

� blood pressure failing to increase by 20 mm Hg97,99 or a decrease in bloodpressure of $10 mm Hg;98 and

� development of horizontal or down-sloping ST-segment depression($1 mm in men, $2 mm in women)97 or ST-segmentdepression $ 5 mm measured 80 msec after the J point.98

For patients with negative stress test results, outcomes may still notbe benign, with the associated risk for symptom onset as well as sud-den death.5,100 In patients with moderate or severe AS, an increase inmean gradient of$18 to 20 mmHg during exercise testing predicts ahigher risk for progression to symptoms and adverse events.98,99 Totest the hypothesis that TAVR in asymptomatic patients mayimprove long-term outcomes compared with watchful waiting, theEarly-TAVR clinical trial (ClinicalTrials.gov identifier NCT03042104)is currently enrolling.

Detection of Associated Ventricular and ValvularAbnormalities

An essential part of the evaluation of every patient with AS is theassessment of chamber sizes, ventricular function, and concomitantvalvular disease.

In chronic AS, changes in LV geometry are both adaptive and path-ologic. As the pressure overload increases, an increase in wall thick-ness maintains normal wall stress and EF. Both an increase in wallthickness with normal LVmass (concentric remodeling) and increasedLV mass (concentric hypertrophy) are frequently seen. Increased wallthickness in AS has been associated with impaired calcium handling,cytoskeletal changes, apoptosis, and increased collagen fiber deposi-tion. These changes result in detectable reduced deformation charac-teristics and chamber compliance, before any change in EF. Thiscascade of events eventually leads to decreased stroke volume andincreased filling pressure, resulting in heart failure with preservedEF. Thus strain imaging as well as diastolic function parameters maybe early markers of abnormal LV function. Importantly, theEuropean Association of Cardiovascular Imaging and AmericanSociety of Echocardiography consensus on the standardization ofstrain imaging defines deformation imaging terminology, the type ofstored data that are used for quantitative analysis, the modality ofmeasuring basic parameters, the definitions of parameters, and the re-sults output with the aim of reducing intervendor variability.101

Ejection Fraction. Long-standing severe pressure overload, partic-ularly in the setting of concomitant hypertension,13,102 often leads toreduced LVEF and cardiac output. Numerous studies havedocumented an increase in mortality associated with reduced EF, aswell as poor renal function in the setting of severe, symptomatic ASirrespective of an intervention on the aortic valve.103,104 A recentmeta-analysis of 26 studies and nearly 6,900 patients showed that pa-tients with baseline low EF and severe AS have higher mortalityfollowing TAVR comparedwith those with normal EF, despite a signif-icant and sustained improvement in LV function.105

Strain Imaging. In the presence of normal EF, increasing severity ofAS was associated with reduced global longitudinal strain(GLS).106,107 GLS was found to be a predictor of all-cause mortal-ity,108,109 and GLS was a superior predictor of outcomes in patientsreferred for surgery compared with standard predictors such as riskscore, presence of ischemic heart disease, and EF.110 In patients withlow flow, low gradient, and preserved EF, GLS was independentlyassociated with survival after aortic valve replacement.111 In patientswith low flow, low gradient, and reduced EF, stress GLS measuredduring dobutamine stress echocardiographymay provide incrementalprognostic value beyond GLSmeasured at rest.112 Three-dimensionalGLS may be a better predictor of outcome compared with 2Dstrain.113 In patients with moderate or severe AS and concomitantcoronary disease, worse apical and mid longitudinal strain parameterswere predictive of significant coronary stenosis.114

Strainmay become a useful predictor of preclinical disease severity.Recent studies have suggested that conservative management of pa-tients with severe but asymptomatic AS may result in poor out-comes.100 In a propensity-matched, prospective study, Taniguchiet al.100 showed that the cumulative 5-year incidence of all-causedeath and heart failure hospitalization was significantly lower in theinitial valve replacement group than in the conservative group(15.4% vs 26.4% [P = .009] and 3.8% vs 19.9% [P < .001], respec-tively). Because mortality is significantly associated with symptomdevelopment,95 strain has been postulated as a possible early marker

http://ClinicalTrials.gov


of ventricular dysfunction in asymptomatic patients with severe ASand thus may be a useful tool in determining the timing of interven-tion in this population. Carasso et al.115 showed that longitudinal strainwas low in asymptomatic patients with severe AS with supernormalapical circumferential strain and rotation. In symptomatic patients,however, longitudinal strain was significantly lower, with no compen-satory circumferential myocardial mechanics. Other investigatorshave suggested that after adjusting for AS severity and EF, only basallongitudinal strain (and not GLS) was an independent predictor ofsymptomatic status.116,117 In fact, following TAVR, the improvementin GLS may be a result of basal and mid segment improvementonly.118

Diastolic Function. The effect of LV diastolic function on outcomein AS is controversial. Biner et al.119 showed that in patients with symp-tomatic severe AS with LV systolic dysfunction (LVEF # 50%) orasymptomatic severe AS with preserved LV systolic function(LVEF > 50%), there was significantly higher 1-year survival rate in pa-tients with E/e0 ratios < 15 compared with those with E/e0 ratios$ 15among both asymptomatic and symptomatic patients. Higher in-hospital mortality or major morbidity may also be associated withan elevated E/e0 ratio.120 Other studies have shownmarked improve-ments in diastolic function parameters following intervention121 butfailed to show an association between baseline diastolic functionand outcomes.122

Concomitant Valve Disease. Additional valve disease may alsoaffect outcomes following TAVR. Studies from the surgical literaturehave been conflicting with regard to treatment of coexistent signifi-cant mitral regurgitation (MR) and AS.123,124 Barbanti et al.125 foundmoderate or severe mitral MR in about 20% of patients in thePlacement of Aortic Transcatheter Valves (PARTNER) IA cohort atbaseline. MR improved in 69.4% of surgical aortic valve replacementpatients and 57.7% of TAVR patients.125 It was uncommon to seeworsening of MR following intervention. An increase in mortality at2 years with moderate or severe MR was seen only in the surgicalaortic valve replacement cohort (49.8% vs 28.1%; adjusted hazard ra-tio [HR], 1.73; 95% CI, 1.01–2.96; P = .04), with no adverse out-comes seen in the TAVR cohort. Persistent moderate or severe MRdid not affect LV remodeling.

Significant tricuspid regurgitation (TR) may also affect outcomes.Of the patients in the PARTNER IIB cohort, 26.6% had moderateor severe TR at baseline. Compared with patients with less thanmoderate TR, these patients had lower LVEF and stroke volumeindex, larger left atrial size, and greater prevalence of moderate orsevere MR. In addition, these patients had larger right atria andventricles, with worse right ventricular function and higher rightventricular systolic pressure estimates. More severe TR was associ-ated with increased 1-year mortality (P < .001), as were right atrialand right ventricular enlargement and right ventricular dysfunction(P > .001). At 30 days, about 30% of patients with baseline moder-ate or severe TR improved to less than moderate TR, and thisimprovement was associated with improved survival at 1 year. Inpatients with concomitant moderate or severe MR, moderate orsevere TR was not associated with increased hazard of deathcompared with less than moderate TR. In patients with minimalMR, multivariate adjustment continued to show that severe TRwas associated with increased mortality (HR, 3.20; 95% CI, 1.50–6.82; P = .003) along with right atrial and right ventricular enlarge-ment (P < .001).

IMAGING FOR TAVR

An effective imager on the heart team must understand the anatomyrelevant to the device and the procedural steps for device implanta-tion, because at each stage of the procedure there are different rolesfor imaging. Table 3 shows some of the commercially available as wellas investigational THV devices with important valve composition andconsiderations. Multimodality imaging used in a TAVR program in-volves the use ofMSCT, cardiacmagnetic resonance imaging, fluoros-copy, and echocardiography, with the ultimate goals of appropriatepatient selection, procedural guidance, and detection of complica-tions. AlthoughMSCT has become a standard preprocedural imagingmodality for measurement of the aortic annular area and perim-eter,126,127 vascular access, coronary artery position, calciumburden, and fluoroscopic projection angles,128 the dynamics of theprocedural environment are unique and require constant communi-cation and adaptability, for which echocardiography is the optimal im-aging modality. Intraprocedural echocardiographic findings must beinterpreted in the context of patient’s hemodynamics, influenced bythe presence of anesthesia and by the procedure itself, and decisionsmust be made in real time, after careful consideration and delibera-tion of all aspects of risks and benefits. Intraprocedural transesopha-geal echocardiography (TEE), with the added value of real-time 3Dimaging techniques, provides an undisputed wealth of continuous,physiologic information both in procedural planning and guidanceand in detecting complications. In this section we highlight some ofthe unique benefits of intra-procedural TEE in patients undergoingTAVR.

Predeployment Imaging

The comprehensive intraoperative preprocedural evaluation is sum-marized in Table 4. Preprocedural assessment of aortic root anatomyand dimensions is paramount to the selection of the appropriate pros-thesis. Several factors are considered when selecting an optimal pros-thetic valve for a patient: aortic annulus and geometry, aortic root andLVOT anatomy, angulation of the aorta (aortoventricular angle), cor-onary height, and amount and distribution of calcification.129

Undersizing a prosthetic valve may lead to PAR or device emboliza-tion, while oversizing may result in aortic root rupture, coronary ostiaocclusion, or conduction abnormalities. Evaluation of the aortic rootstarts with measurement of the aortic annulus. Various vendor-specific annular measurement packages measure maximum and min-imum diameters, perimeter, and area of the aortic annulus. Althoughthe word annulus implies a circular structure, there is no histologic oranatomic boundary to define it and to guide measurement. Rather,the measurements are performed in a virtual plane defined by the na-dirs of the semilunar leaflet attachments. Traditionally, the aorticannulus has been described by a single measurement from 2D trans-thoracic echocardiography (TTE) or TEE. However, the three-dimensionality and the complexity of the aortic root anatomy canbe adequately appreciated only by using a 3D imaging modality.This has been investigated in studies that showed that the incidenceof more than mild PAR was significantly lower when sizing of theaortic annulus was performed using MSCT compared with sizing per-formed by 2D echocardiography.130,131 Two-dimensionalechocardiography consistently underestimates the size of the aorticannulus for several reasons: (1) a linear dimension assumes acircular geometry of the annulus, while a growing body of literature

Table 3 Examples of THVs commercially available or in trials

Transcatheter valve name (manufacturer) Example Features Procedural/imaging nuances

SAPIEN 3 (Edwards Lifesciences),

commercially available

� Cobalt chromium frame

� Bovine pericardial leaflets

� PET cuff

� Balloon-expandable, typicallydeployed during rapid pacing

� Shortens from skirt end

� Positioning by echocardiography

ensures that the aortic end is below

the sinotubular junction and coversthe native leaflets

� May be ideal for high risk for

coronary obstruction and distortedaortic anatomy

� May be appropriate for bicuspid

aortic valve

EvolutPro (Medtronic), commerciallyavailable

� Supra-annular valve position� Porcine pericardial leaflets

� External PET wrap

� Self-expanding frame� Repositionable

� Rapid pacing not required

� Ideal position of the ventricular endonce deployed should be 2–4 mm

below the native annulus (and not

$6 mm)� May be more difficult to accurately

position with a horizontal aorta or

annular/STJ distortion

� May be ideal for preexisting mitralbioprostheses

� Has been used for primary AR

Lotus Edge (Boston Scientific, Natick,

MA), investigational device

� Mechanical expansion of device

� Repositionable before release

� Adaptive Seal skirt� Rapid pacing not required

� Relies on fluoroscopic positioning

with assistance from

echocardiography for paravalvularleak assessment and need for

repositioning

� May be appropriate for bicuspidaortic valve

ACURATE neo (Boston Scientific),

investigational device

� Supra-annular valve

� Self-expanding

� Partially recapturable

� Three stabilizing arches� Rapid pacing not required

� Echocardiographic positioning of

the ventricular end below the

annulus

� Has been used for primary AR

JennaValve (JenaValve, Munich,

Germany), investigational device

� Feeler-guided anatomic

positioning� JenaClip anchoring to native

leaflets

� Retrievable and repositionable� Rapid pacing not required

� Echocardiographic guidance of

anatomic positioning to align clipsand commissures

� Treats primary AS and primary AR

Centera (Edwards Lifesciences),

investigational device

� Self-expandable, nitinol stent with

bovine pericardial tissue valve� Annular position

� PET fabric

� Motorized deployment

� Repositionable and retrievable

� Echocardiography for paravalvular

leak assessment and need forrepositioning

PET, Polyethylene terephthalate; STJ, sinotubular junction.


Hahn et al 9

Table 4 Preprocedural structural and functional assessmentby echocardiography

� Aortic valve and root� Aortic valve morphology

- Confirm pathology

- Assess presence of AR- Number of cusps (bicuspid/tricuspid)

- Volume and distribution of calcifications� Aortoannular complex dimensions

- Aortic annular dimensions (major, minor, and averagediameters, perimeter, area)

- Sinuses of Valsalva diameter

- Sinotubular junction diameter

- Aortic annulus to coronary artery ostia distances� Aortic valve hemodynamics

- Aortic valve peak velocity, peak and mean gradients, and

calculated valve area- Dimensionless index

- Stroke volume and stroke volume index� LVOT

- Extent and distribution of calcium- Presence of sigmoid septum and dynamic narrowing

� Mitral Valve� Severity and mechanism of MR� Presence of mitral stenosis� Severity of ectopic calcification of the anterior leaflet

� LV size and function� Exclude intracardiac thrombus� Wall motion assessment� EF� Stroke volume and cardiac output

� Right heart� Right ventricular size and function� Tricuspid valve morphology and function� Estimate of pulmonary artery pressures

� Presence of pericardial effusion

igure 4 Multiplanar reconstruction of a 3D data set by twoethods. (A) Multiplanar reconstruction of the virtual annularlane (red box) obtained by aligning the long-axis transverselane (green box) and coronal plane (blue box). The annulusmeasured by direct planimetry. (B) Indirect planimetry

ethod, which uses a mitral valve software package, QLABVQ software (Philips Medical Systems, Andover, MA), thus

ricking the system into measuring the aortic annulus as if itere a mitral annulus. The top two quadrants of (B) showhe positioning of the ‘‘anterior’’ (A), ‘‘posterior’’ (P), ‘‘postero-edial’’ (PM), and ‘‘anterolateral’’ (AL) annular indicators. Onuccessive rotations of the two orthogonal long-axis planesreen and red boxes), the annular plane is identified and auto-atically shown in the annular short axis of the blue plane (blueots). The complete the annular plane is created without actu-lly planimetering on the annular short axis and is thus an ‘‘in-irect’’ planimetric method. Both methods yield the annularrea, perimeter, and maximum and minimum dimensions ofhe annulus.


has shown that it is nearly uniformly oval shaped132,133; (2) the long-axis or sagittal plane in which the measurement is performed may benot bisect themaximum dimension of the annulus (i.e., imaging of thehinge point to hinge point rather than hinge point to fibrous trigone);and (3) the measurement in the long-axis view generally representsthe smaller diameter of the noncircular annulus.

Three-dimensional echocardiography overcomes the limitations of2D imaging by allowing measurements of the annular area and perim-eter. Although 3D TTE lacks the spatial resolution for adequate mea-surements of the aortic root, several recent studies have shown thatmeasurements performed by multiplanar reconstruction of 3D transe-sophageal echocardiographic data sets yields comparable results withthose obtained using MSCT, at the same time avoiding the risks asso-ciated with exposure to radiation and contrast dye.50,134,135

Multiplanar reconstruction of a 3D data set facilitates directmeasurements of the major and minor diameters, as well as annulararea and perimeter from an on-axis short-axis plane (Figure 4A).Other investigators have used vendor-specific software originally de-signed for the mitral valve to indirectly planimeter the annulus136

(Figure 4B) and proved that annular measurements by both 3D TEEand MSCT predicted mild or greater PAR with equivalent accuracy.51

Besides dimensions of the aortic annulus, other measurements ofthe aortoannular complex should be performed, such as the size ofthe sinuses of Valsalva, diameter of the aorta at the sinotubular

FmppismMtwtms(gmdadat

Figure 5 Left coronary artery height measured by multiplanar reconstruction. Because the left coronary artery lies in the coronalplane, imaging of the height of the left main coronary artery requires 3D imaging and reconstruction. In the multiplanar reconstruction(A), the blue plane is first aligned along the long axis of the aorta from the sagittal (red) plane. Second, the blue plane is aligned in thetransverse (green) plane with the left coronary artery (red arrow). The coronal (blue) plane is now the plane of the left coronary artery(red arrow). This blue plane (B) is then used to measure the distance from the hinge point of the left coronary cusp to the left coronaryorifice (red arrow) as well as the length of the left coronary cusp (green arrow).

Table 5 Intraprocedural structural and functional TEE

� Positioning of wires (pacer, pigtail and guidewire) � May facilitate crossing the aortic valve

� Identify entrapment in the mitral valve apparatus

� Exclude presence of new/worsened pericardial effusion� Identify thrombus on wires or catheters

� Balloon aortic valvuloplasty � Evaluate relationship of leaflet calcification with the aortic root walls

� Exclude presence of new/worsened pericardial effusion

� Exclude presence of new/worsened MR� Evaluate mobility of aortic valve cusps and severity of AR

� Exclude new wall motion abnormalities, or confirm flow by color flow Doppler in the

coronary arteries

� Positioning and deployment of transcatheter valve � Balloon-expandable valve� Confirm the aortic end position of the balloon-expandable transcatheter valve

below STJ and covering leaflets� Watch displacement of calcium for risk for rupture or coronary occlusion duringcontrolled balloon inflation

� Self-expanding valve� Confirm the ventricular end position of the self-expanding transcatheter valve

2–4 mm below the annular plane� Confirm final position once released

� Transapical cannulation � Confirm site of transapical puncture (away from the interventricular septumand right

ventricle)� Evaluate retrograde position of the guidewire through the aortic valve

� Exclude entrapment in the mitral valve apparatus and worsened MR

� Post-deployment assessment � Assess the transcatheter valve� Position, shape, peak/mean gradient, and AVA

� Presence of central or paravalvular regurgitation

� Patency of coronary arteries

� Presence of pericardial effusion or focal rupture� Assess ventricular and other valvular function

STJ, Sinotubular junction.


Hahn et al 11

junction, and the distance of the coronary artery ostia from theannulus.129 Because the left coronary artery ostium lies in the coronalplane, the coronary height can be measured only by multiplanarreconstruction (Figure 5). Data from a large multicenter registry ofcoronary obstruction after TAVR, showed the left coronary arterywas most commonly involved (88.6%), with lower mean left

coronary artery ostia height (10.6 6 2.1 vs 13.4 6 2.1 mm,P < .001) and sinus of Valsalva diameter (28.1 6 3.8 vs31.9 6 4.1 mm, P < .001) compared with control subjects.9 The dis-tribution of calcium in the aortic root, extension into the LVOT andaortomitral curtain, and proximity of calcium to the coronary arteryostia should also be described. LVOT morphology with the presence

Figure 6 Fluoroscopic imaging during TAVR. (A) Fluoroscopic image of the wires shows the relative positions of the pigtail catheter inthe right coronary sinus of Valsalva, as well as the pacing wire in the right ventricle and guidewire in in the left ventricle. (B) Fluoro-scopic image during maximum balloon inflation. In this image of maximal balloon inflation, the calcific left coronary cusp can beimaged occluding the left main coronary artery. In addition, contrast injection reveals significant leak around the undersized balloon,indicating a risk for paravalvular regurgitation.


of basal septal hypertrophy as well as the presence of midventricularhypertrophy is important to assess, as the development of subvalvulardynamic obstruction with hemodynamic instability after valvedeployment has been described.137

Intraprocedural Imaging

Procedural guidance can be ensured through a combination of imag-ing modalities such as fluoroscopy, aortography, and echocardiogra-phy. The significant advantage of TEE is continuous monitoring ofall aspects of the procedure. In situations of acute hemodynamicchanges, TEE can readily diagnose complications associated withtransvalvular wire or delivery system or balloon valvuloplasty.Table 5 summarizes intraprocedural imaging with TEE.

Several wire positions are typically confirmed by fluoroscopy(Figure 6A) but may also be imaged by echocardiography. Theseinclude the pacing wire in the right ventricular apex, the transvalvularstiff guidewire within the left ventricle, and the pigtail catheter placedin the sinuses of Valsalva at the level of the noncoronary cusp (for self-expanding valves) and right coronary cusp (for balloon-expandablevalves). Placement of wires can lead to thrombus formation, ventric-ular perforation, and accumulation of pericardial effusion as well asdisruption of mitral valve apparatus with worsening MR.

Before positioning of the valve, predilation of the aortic valve maybe performed with balloon aortic valvuloplasty and rapid ventricularpacing during inflation. Besides facilitating subsequent transvalvularpositioning of the delivery system, radiographic contrast opacificationof the root during balloon aortic valvuloplasty provides useful infor-mation regarding possible coronary ostia occlusion by native leafletsor calcifications and appropriate sizing of the valve by visualizationof the leak around the maximally inflated balloon (Figure 6B).Although hemodynamic instability may occur because of rapid ven-tricular pacing, other causes of hemodynamic instability should beruled out after balloon deflation: pericardial effusion and tamponadedue to aortic root rupture, severe left or right ventricular dysfunctiondue to acute coronary occlusion, or severe acute aortic regurgitation(AR).24

It is imperative that the transcatheter valve be positioned preciselyaccording to vendor-specific recommendations. High implantation(too aortic relative to the annulus) may result in transcatheter valveembolization into the aorta, aortic intima injury, AR, or coronary ar-tery ostia obstruction. Low implantation (too ventricular relative tothe annulus) may result in disturbance of the mitral valve apparatusand MR, impingement on the atrioventricular node and conductionabnormalities, or transcatheter valve embolization into the ventricle.Although the landing zone is standardized and depends on the typeof the valve (Table 3), each case is individualized on the basis of thesize of the transcatheter valve, anatomy of the aortic root andLVOT, and position of the left coronary artery. Although fluoroscopyplays a pivotal role in positioning the transcatheter valve, TEE can pro-vide complementary information. For the third-generation balloon-expandable SAPIEN 3 (Edwards Lifesciences, Irvine, CA), the finalimplantation depth should be 1 to 2 mm below the native aorticannulus.24 Because the design of the valve allows shortening afterdeployment only from the ventricular side, the positioning of thevalve before deployment should focus on the aortic edge, whichshould be covering the native leaflets and remain below the sinotub-ular junction24 (Figures 7A and 7B). For the second-generation self-expandable valve CoreValve Evolut R (Medtronic, Minneapolis,MN), an optimal implantation depth is 2 to 4 mm below the aorticannulus.129 The deployment of the self-expandable valve occurs ina controlled manner, over several minutes. Because of the initialposterolateral orientation of the valve during deployment, the poste-rior edge of the valve is initially higher (more aortic) than the anterioredge (Figure 7C). After full release from the delivery system, the valvepivots, the anterior edgemoves superiorly, and the valve aligns coaxialwith the long axis of the aorta24 (Figure 7D).

Postprocedural Imaging

An assessment of the position of prosthesis, leaflet mobility, and theshape of the deployed valve should be performed immediatelyfollowing TAVR.24 Complications such as coronary occlusion or aorticrupture are typically accompanied by significant hemodynamic

Figure 7 Predeployment and final position of the transcatheter aortic valve. (A) Balloon-expandable valve position before deploy-ment. The aortic edge is below the sinotubular junction and covering the leaflets. After deployment (B), the ventricular edge shouldbe 1 to 2mmbelow the annulus, but the final positionmay depend on the degree of oversizing. (C)Position of the self-expanding valvebefore deployment. The ventricular edges are typically not symmetrically below the annulus (lower anteriorly) but should be 3 to 5mmbelow the annular plane. Following release of the aortic tabs (D), the valve typically pivots, and the anterior edgemoves superiorly andthe valve aligns coaxial with the long axis of the aorta.


Hahn et al 13

compromise. The most common complication following TAVR isPAR, with greater than mild regurgitation seen in 0% to 24% of pa-tients in early experience12,132,138-147 and only 0% to 6% withcurrent valve iterations.2,148-150 Rapid assessment of PAR followingTAVR is essential because this post-TAVR complication can be treatedintraprocedurally with balloon dilatation, valve-in-valve salvage, orparavalvular device implantation.151,152 PAR assessment isparticularly important following deployment of a repositionabletranscatheter valve, but cine angiography and invasivehemodynamics may be challenging because of the atypicalcharacteristics of the regurgitation jets (Table 6).

Echocardiography, either transthoracic or transesophageal, re-mains the preferred method for assessing PAR for a number of rea-sons. Echocardiography can identify the location, number, andextent of the regurgitation jets and discriminate between transvalvular(central) and PAR (Figure 8). Importantly, echocardiography can

determine the etiology of PAR: suboptimal valve position, valve un-der- or overexpansion or asymmetry, or ectopic annular or subannu-lar calcification. The assessment of location and etiology willdetermine the appropriate intraprocedural management of thiscomplication: valve-in-valve for central AR and postdilatation, PARclosure with a leak device, or valve-in-valve. It is important to scanfrom distal (aortic) to proximal (ventricular) ends of the THV to iden-tify jet locations and direction. Central prosthetic AR jets will occur atthe level of leaflet coaptation, whereas paravalvular regurgitation willbe seen at the proximal (ventricular) edge of the THV. Multiple short-axis views with images adjusted to yield the highest frame rates shouldinclude the LVOT immediately proximal to the stent (to confirm thatjets reach the left ventricle; Figure 9).

Amajor limitation of assessment of PAR in the short-axis views of thetranscatheter valve with 2D imaging and color flow Doppler, be it byTTE or TEE, is that the scan plane may not be at the level of the origin

Table 6 Limitations of other intraprocedural imaging modalities for assessing PAR

Cine angiography Hemodynamic parameters

Dependent on

� Observer’s experience

� Intensity of fluoroscopy

� Volume of contrast injected� Type and position of catheter tip140

Inability to differentiate intra- from paravalvular regurgitationExposure to radiation

Exposure to angiographic contrast

Limited accuracy and reproducibility153

Inability to differentiate intra- from paravalvular regurgitation

Influenced by abnormal ventricular and aortic compliance

Dependent on heart rate

Significant overlap between grades of regurgitation140

Figure 8 Imaging of paravalvular aortic regurgitation. Paravalvular aortic regurgitation should be assessed by multiple parameters,and from multiple imaging planes. Panel (A) is the short-axis view showing that the regurgitant jet likely arises from the commissurebetween the left and noncoronary cusps (white arrow). Panel (B) is the long-axis view imaging the proximal convergence zone(white arrow) and panel (C) is the transgastric view with the jet area well-imaged. Importantly, the severity of regurgitation shouldnot be assessed by jet area or length. The relatively short pressure halftime (D) can be a result of abnormal ventricular or aorticcompliance and is less diagnostic in this patient population.


of the regurgitation; too low (ventricular) a scan plane will overestimatethe severity of regurgitation by imaging jet spray,while toohigh (aortic) aposition may mistake flow in the sinuses of Valsalva for regurgitation.Compared with TTE, TEE provides not only higher quality 2D imagesbut also high-quality 3DcolorDopplerdata sets,which allowplanimetryof the vena contracta area (Figure 10). Three-dimensional TEE has alsoprovidedmore insight into some of the risk factors associatedwith trans-valvular regurgitation. Shibayama et al.154 showed that a more ellipticalshape of the prosthetic valve at the commissural level, a larger prostheticexpansion, and antianatomic orientation of the prosthetic valve

(prosthetic valve commissures at$60� comparedwith the native aorticvalve commissures) were associated with transvalvular regurgitation. Ifthe imaging plane is above the stent, regurgitationmay not be visualized,or color flow within the sinuses of Valsalva just above the annulus maybe mistaken for regurgitant jets below the transcatheter valve. In addi-tion, color Doppler ‘‘twinkling artifacts’’155 occur over strongly reflectivesurfaces such as the metal frame of the transcatheter valve and can bemistaken for regurgitation; these artifacts are pancyclic, and spectralDoppler of these color signals will show nonphysiologic signals(Figure 9A).

Figure 9 Imaging of PAR. Color Doppler ‘‘twinkling artifact’’ isseen over the entire metal frame of the transcatheter valve insystole (as well as diastole). (A) Multiple short-axis views withimages adjusted to yield the highest frame rates should sweepfrom the midtranscatheter valve (B) to assess for central regur-gitation, as well as the LVOT immediately proximal to the stent(C) to confirm that jets reach the left ventricle. SOV, Sinuses ofValsalva.


Hahn et al 15

A multiparametric and multiwindow approach based on theintegration of multiple indices has been proposed by the ValveAcademic Research Consortium (VARC) 2 for the assessment ofPAR with a recommendation for a three-class scheme (mild, mod-erate, and severe).156 In a series of 1,255 consecutive 2D transtho-racic echocardiographic examinations from five TAVR registries, a

combination of the VARC-2 parameters was feasible in only 53%of the cases. In 40% of cases, AR after TAVR was graded on thebasis of a single reliable VARC-2 criterion supported by non-VARC parameters, and in 7% of cases, post-TAVR AR was gradedon the basis of non-VARC parameters.157 Several other studieshave raised the same concern of inconsistencies and variabilityin assessment of PAR across different core laboratories and be-tween different studies,158,159 particularly given the limitations ofechocardiography (Table 7).

To improve overall feasibility and accuracy in grading PAR, aunifying five-class scheme using qualitative, semiquantitative andquantitative parameters that have emerged from trials and guide-lines has been proposed (Table 8).160 This more granular schemewould ensure more flexibility for the ‘‘between-grades’’ regurgita-tion jets but would also allow collapsibility and reporting withinthe three-class scheme recommended by VARC-2: mild andmild to moderate would become mild, and moderate and moder-ate to severe would become moderate. The ability of this gradingscheme to predict outcomes after TAVR has recently been studied.In a retrospective, single-center study, Jones et al. found anapparent stepwise increase in mortality for each grade of AR at1 year, even after controlling for age, gender, Society ofThoracic Surgeons score, baseline LVEF, and AR before TAVR,with a unit HR of 2.26 for each 1+ increase in AR after TAVR(95% CI, 1.48–3.43; P < .001). There was a twofold increase inmortality at 1 year for patients with mild AR (1+ and 1 to 2+)compared with those with trivial to 1+ AR.161 The PARTNER IItrial also used the grading scheme and showed that mild andmild to moderate PAR was not associated with worse outcomescompared with no or trace PAR.162

A summary of the elements of a comprehensive postproceduralexamination is presented in Table 9. Although most aortic root in-juries are catastrophic, some are insidious, with slow accumulationof a pericardial effusion and delayed presentation with tamponadephysiology.163 A high level of alertness and suspicion for excludingstructural injury as a cause of hemodynamic instability is requiredat all stages of the procedure. Postprocedural iatrogenic ventricularseptal defect has been described, and routine interrogation of theinterventricular septum, particularly at the perimembranous level,should be performed.164

PROCEDURAL AND POSTPROCEDURAL IMAGING

WITH TTE

Although the initial TAVR trials mandated use of general anesthesia(GA) and intraprocedural TEE, the standardization of the procedurehas led to the use of other forms of anesthesia. Sedation withoutintubation can be performed with an anesthesiologist (monitoredanesthetic care) or without (conscious sedation [CS], also knownas the ‘‘minimalist approach’’).165,166 These approaches limit theability to perform intraprocedural TEE and rely instead onTTE.167 The advantages and disadvantages of TTE versus TEE arelisted in Table 10.168 The benefits of this new approach haveincluded lower use of intensive care units, shorter length of stay,and lower cost. This must be weighed against the reports of possiblehigher paravalvular regurgitation rates,169,170 nephrotoxic contrastagent use,171,172 and the increased morbidity of conversion to GAwith CS and TEE.173 Some centers have continued to use GAand TEE but with a ‘‘fast track’’ algorithm that has shortened length

Figure 10 Three-dimensional data set of the PAR imaged in Figure 8. Multiplanar reconstruction allows the alignment of the short axisof the vena contracta (red plane), which can be planimetered for an estimate of regurgitant severity. In this case, despite the pressurehalf-time of 258 msec, this jet represents mild paravalvular regurgitation.

Table 7 Limitations of echocardiographic techniques and parameters for assessing paravalvular regurgitation

Echocardiographic parameters Pitfalls

Structural parameters� Depth of implantation (ME AV LAX, TG LAX,

deep TG five-chamber view)

� Configuration of the deployed valve (ME AV SAX)

� Presence of artifacts (e.g., acoustic shadowing, side lobe)� Unclear location of the imaging plane in the short-axis views (e.g., too ventricular or

too aortic)

Color Doppler parameters (ME AV LAX, TG LAX,deep TG five-chamber, ME AV SAX)

� Vena contracta width

� Vena contracta area

� Circumferential extent

� Multiple jets with origins at different levels� Eccentric jets, tangential to the aortic annular plane

� Presence of artifacts (e.g., twinkling, acoustic shadowing)

� Unclear location of the imaging plane in short axis (e.g., too ventricular or too aortic)

� Irregularity of the regurgitation orifice

Doppler and quantitative parameters

� Pressure half-time

� Aortic holodiastolic reversal of flow� Regurgitant volume

� Regurgitant fraction

� Dependent on ventricular and aortic compliance

� Dependent on heart rate and systemic blood pressure

� Significant inter- and intraobserver variability for quantitative parameters

3D imaging � Highly dependent on operator experience� Low spatial and temporal resolution, especially for 3D color data sets

LAX, Long-axis; ME, midesophageal; SAX, short-axis; TG, transgastric.


Table 8 Unifying scheme for grading the severity of paravalvular regurgitation

Three-class grading scheme Trace Mild Moderate Severe

Unifying five-class grading

scheme Trace Mild Mild to moderate Moderate Moderate to severe Severe

Cine angiography

Grade 1 Grade 1 Grade 1 Grade 2 Grade 3 Grade 4

Invasive hemodynamics

AR index‡ >25 >25 >25 10–25 10–25 <10

Doppler echocardiography

Structural parameters

� Valve stent Usually normal Usually normal Normal/abnormal† Normal/abnormal† Usually abnormal† Usually abnormal†

� LV size§ Normal Normal Normal Normal/mildly

dilated

Mildly/moderately

dilated

Moderately/severely dilated

Doppler parameters

(qualitative or

semiquantitative)

� Jet features

Extensive/wide jetorigin

Absent Absent Absent Present Present Present

Multiple jets Possible Possible Often present Often present Usually present Usually present

Jet path visiblealong the stent

Absent Absent Possible Often present Usually present Present

Proximal flow

convergence visible

Absent Absent Absent Possible Often present Often present

� Vena contracta width

(mm)*: color Doppler

<2 <2 2–4 4–5 5–6 >6

� Vena contracta area

(mm2)k: 3D colorDoppler

<5 5–10 10–20 20–30 30–40 >40

� Jet width at its origin

(%LVOT diameter):color Doppler*

Narrow (<5) Narrow (5–15) Intermediate (15–30) Intermediate (30–45) Large (45–60) Large (>60)

� Jet density: CW

Doppler

Incomplete or faint Incomplete or faint Variable Dense Dense Dense

� Jet deceleration rate

(PHT, msec): CW

Doppler‡,§

Slow (>500) Slow (>500) Slow (>500) Variable (200–500) Variable (200–500) Steep (<200)

� Diastolic flow reversalin the descending

aorta: PW Doppler‡,§

Absent Absent or briefearly diastolic

Intermediate Intermediate Holodiastolic (end-diastolicvelocity > 20 cm/sec)

Holodiastolic (end-diastolicvelocity > 25 cm/sec)

(Continued )

Journalo

ftheAmerican

Society

ofEchocard

iograp

hy

Volume-

Number

-

Hahnet

al17

� Circumferential extent

of PAR (%): color

Doppler

<10 <10 10–20 20–30 >30 >30

Doppler parameters

(quantitative)� Regurgitant fraction (%) <15 <15 15–30 30–40 40–50 >50� Effective regurgitant

orifice area (mm2){<5 <5 5–10 10–20 20–30 >30

CW, Continuous-wave; PHT, pressure half-time; PW, pulsed-wave.

Source: Pibarot et al.160

� Parameters that are most frequently applicable and used to grade PA severity by echocardiography.� Parameters that are less often applicable because of pitfalls in the fe ibility or accuracy of the measurements and/or to the interaction with other factors.

*These parameters are generally assessed visually.†Abnormalities of stent position (too low or too high), deployment, and r circularity.‡These parameters are influenced by LV and aortic compliance. Hence, ow transvalvular end-diastolic aorta–to–LV pressure gradient due to concomitant moderate or severe LV diastolic

dysfunction may lead to false-positive results. The high dependency of a rtic flow reversal on aortic compliance considerably limits the utility of this parameter in the elderly population un-

dergoing TAVR. These parameters are also influenced by chronotropy.§Applies to chronic PAR but is less reliable for periprocedural or early p stprocedural assessment.kThe vena contracta area is measured by planimetry of the vena contra ta of the jet(s) on 2D or 3D color Doppler images in the short-axis view.{The effective regurgitant orifice area is calculated by dividing the regu itant volume by the time-velocity integral of the AR flow by CW Doppler.

Table 9 Comprehensive echocardiographic assessment follow ng TAVR

Chamber Transcatheter valve

Structure � LV dimensions and volume, wall thic ess, mass

� Right ventricular dimensions (diastoli ), wall thickness, function

� Position in relation to the annulus

� Stability/motion of the transcatheter valve

� Expansion/shape and regions of separation from the annulus

Function � Regional wall motion abnormalities� EF

� Leaflet motion including an assessment of opening as well as closure

Hemodynamics � LV stroke volume

� Right ventricular stroke volume (for P R assessment)� Pulmonary artery pressure

� Peak transaortic velocity

� Peak and mean transaortic gradient� AVA

� Regurgitant severity and location

Other � Concomitant other valve disease � Impingement or compromise of adjacent anatomic structures

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Table 10 Strengths and weaknesses of TTE versus TEE

Parameter TTE TEE

Sedation during TAVR � None required (sedation for procedure only) � GA, monitored anesthetic care or CS

Imaging advantages � Standard windows for assessing ventricular and

valvular structure and function

� Higher resolution with high frame rates for 2D and 3D

imaging� Continuous imaging throughout procedure,

irrespective of access route

� Preprocedural imaging may avoid complications

(i.e., paravalvular regurgitation, annular/aorticrupture, coronary occlusion)

� Immediate intraprocedural diagnosis of

complications

Imaging disadvantages � Image quality dependent on patient factors (i.e.,

chest morphology, lung hyperinflation, suboptimal

patient positioning)

� Procedural delay during image acquisition (tominimize radiation exposure to imager)

� Noncontinuous imaging during procedure

� Low resolution with low frame rates for 2D and 3D

imaging� Limited imaging windows for nontransfemoral

access routes

� Image quality dependent on patient factors (i.e.,

calcific acoustic shadowing, cardiac position relative

to esophagus and stomach)

� Probe interference with fluoroscopic imaging(minimized by articulation of probe)

Other advantages � Early recovery and discharge � Need for postprocedural monitoring (may not bedifferent than for TTE)

Other disadvantages � Possible higher radiation exposure to imager

� Interference with sterile field

� Trauma to oropharynx, esophagus, or stomach


Hahn et al 19

of intensive care unit and hospital stays, as well as reduced cost.174

A Brazilian registry, however, found that the use of TEE to monitorthe procedure was a protective factor against overall (HR, 0.57) andlate (HR, 0.47) mortality.175

Nonetheless, numerous recent reports of the safety of TAVRunder monitored anesthetic care or CS165,176 have resulted inthe increasing use of this management protocol.177 TheEuropean Society of Cardiology’s Transcatheter Valve Treatmentregistry found that survival at 1 year, compared using Kaplan-Meier analysis, was similar between groups (log-rankP = .1505), although in the highest tertile logistic EuropeanSystem for Cardiac Operative Risk Evaluation score group, GApatients had higher mortality. Interestingly, GA patients had ahigher immediate procedural success rate and a lower rate ofperiprocedural complications, and CS patients had a strong trendtoward higher combined (myocardial infarction, major stroke, andin-hospital death) adverse event rate (7.0% with CS vs 5.3% withGA, P = .053).178

Baseline patient characteristics as well as site experience likely in-fluence the outcomes of the GA and CS approaches. Condadoet al.179 studied the GA and CS approaches in patients with chronicobstructive pulmonary disease and showed no differences in pro-cedure complications and 30-day mortality between GA and CS pa-tients with multivariate analysis, showing that the minimalistapproach was associated with improved 1-year survival (HR, 0.28;95% CI, 0.08–0.97). Importantly, similar procedural and short-term outcomes with CS have been seen at some high-volumesites180; the first CS procedure in this study was performed after300 GA studies. Further studies should be performed as the fieldbegins to address TAVR in the lower risk patient population, whoare also at lower risk for GA complications and whose expected

outcomes are significantly better than patients treated in these reg-istries.2,148

Transthoracic Echocardiography

Immediate and accurate interpretation of transthoracic echocardio-graphic images typically requires the presence of a physician echo-cardiographer in a TAVR suite. Proper training and experience inperforming these studies is mandatory.168 All transthoracic imagingrequires direct placement of the probe within the fluoroscopic imag-ing plane, with possible high exposure to radiation; a team approachis thus needed, because TTE should not be performed during simul-taneous fluoroscopy. A standard imaging protocol should be fol-lowed if time permits, but frequently a limited, focused study iswarranted.

Baseline Transthoracic Assessment. A standard imaging pro-tocol should assess ventricular size and function and valvular func-tion (aortic, mitral, tricuspid, and pulmonic). Baseline assessmentof cardiac function is essential to identify ideal imaging windowsand allow assessment of changes following the procedure or duringhemodynamic compromise. The supine position and avoidance ofthe sterile field may prohibit proper transducer placement, and a‘‘low’’ parasternal window may be necessary (Figure 11). Althougha low parasternal view is not recommended for measurements ofthe left ventricle, in the elderly population it is frequently ideal forimaging the LVOT, annulus, and aortic root. The use of simulta-neous multiplane imaging can be helpful, but the significantlyreduced frame rates with this 3D imaging modality may limit its util-ity for color Doppler assessment of flow. The usual ultrasound inter-ference rules still apply, such as chest wall deformities, emphysema,

Figure 11 Transthoracic imaging at baseline from the parasternal long-axis window. (A)Simultaneous biplane image from a ‘‘lowwin-dow’’ imaging plane commonly seen with the patient supine. The orthogonal short-axis view at the level of the LVOT shows bulkycalcium (yellow arrow) protruding into this space. (B) Use of simultaneous multiplane imaging of the aortic valve (yellow circle)with very bulky calcification of the right coronary cusp. The dashed white arrow on the long-axis (left) view shows the level of imagingfor the orthogonal short-axis (right) view.


and obesity. In addition, parasternal windows may be limited forassessment of PAR in the setting of posterior annulus shadowingby the THV and the direction of the regurgitant jet perpendicularto the ultrasound beam.

Intraprocedural Assessment. Imaging during valve implanta-tion can be performed if the imager and interventionalists worktogether to eliminate unnecessary radiation exposure to the imager.Table 11 summarizes the transthoracic echocardiographic imagingrecommendations during TAVR. It is possible to image wires, cathe-ters, and the stented valve; thus, on occasion, TTE may be used toconfirm the position of the stiff wire, pacing wire, or even transcath-eter valve.

Immediately after valve deployment, TAVR stent positioning,shape, and leaflet motion can rapidly be assessed with imaging in

biplane mode. The parasternal long-axis view is best for determiningthe final valve position, but the short-axis view is essential in theassessment of valve shape as well as presence and severity of para-valvular and central AR, as previously discussed. LV and right ven-tricular wall motion should be carefully assessed from parasternaland apical views; changes in function that correlate with a coronarydistribution may indicate an acute coronary obstruction. Apicalviews are also essential for a full hemodynamic assessment of theTHV.

There are a number of caveats to assessing PAR severity intra-procedurally using TTE. First, color Doppler jet length and area, aswell as spectral Doppler pressure half-time (by continuous-waveDoppler) or holodiastolic reversal of flow in the descending aorta(by pulsed-wave Doppler), are significantly influenced by bloodpressure, LV compliance, and aortic compliance. In this elderly

Table 11 Summary of intraprocedural transthoracic echocardiographic imaging recommendations for TAVR

Procedural step Imaging recommendations Example

Stiff wire position 1. Imaging of wire: ensure stable position

in the ventricle without entanglement in

mitral apparatus/worsening MR

2. Exclude perforation and pericardialeffusion

Simultaneous biplane imaging of the wire (yellow arrows

and dashed line)

Positioning oftranscatheter

valve

1. Balloon-expandable valvea. SAPIEN 3: outflow edge of the

transcatheter valve should cover

the native leaflets while being below

the sinotubular junction; optimal finalposition covers the native leaflets

2. Self-expanding valve

a. EvolutPro: edge of the proximal stent

should be 2–4 mm below the annulus

The same parasternal LAX image is shown with the crimpedSAPIEN 3 valve (green arrow in A and green cylinder in B)below the sinotubular junction (yellow arrow in A) butcovering the leaflets (red dashed lines in B)

Immediatepostdeployment

1. Assess stent positioning, shape andleaflet motion; perform comprehensive

hemodynamic measurements including

effective orifice area

2. Assess paravalvular regurgitation usingshort-axis images of the LVOT just

apical to the inflow edge of the valve,

as well as apical views, to confirm jetreaches the ventricle; note that paravalvular

jet length and area are not used to assess

severity of regurgitation but

may be useful to identify the locationand number of regurgitant jets

3. Exclude complications (see Table 12)

Post-TAVR parasternal imaging of the new THV fromlong-axis (A) and short-axis (B) views

Apical views of the transcatheter valve avoids the shadowing that may

limit paravalvular regurgitation assessment from parasternal views

LAX, Long-axis.


Hahn et al 21

Table 12 Complications of TAVR diagnosed by TTE

Complication Transthoracic echocardiographic assessment

Hemodynamic instability

a. Severe transvalvular or PAR � Assess location of regurgitation (central vs paravalvular)

� Assess position of the transcatheter valve� Assess severity of AR

b. Severe MR � Evaluate severity of MR and anatomy of the mitral apparatus: valvular perforation, rupture

chordae, tethering of the leaflets

c. Pericardial effusion � Assess for tamponade physiology and possible etiology (i.e., chamber perforation, aorticdissection)

d. Ventricular dysfunction � Evaluate for regional or global wall motion abnormalities of the left or right ventricle

� Identify the coronary ostium; use color flow Doppler to assess blood flow

e. Aortic rupture or dissection � Examine the aortic root/ascending aorta for periaortic hematoma, aortic dissection, or rupture

� Assess for pericardial effusion/tamponade

f. Major bleeding � Assess ventricular size and function (wall collapse due to hypovolemia)

Other procedural complications

a. Identify thrombus on wires/catheters � When noted, supplemental heparin may be given

b. Malpositioning of the THV � Too high or too lowwithin the annulus with resulting hemodynamic instability: rapid deployment ofa second valve can be performed

� Embolization of the valve (into the left ventricle or into the aorta) may require surgical intervention

c. Fistula/perforation � Ventricular septal defect

� Aortocameral fistula (typically into the RVOT or right atrium)

RVOT, Right ventricular outflow tract.

Figure 12 Acute ventricular septal rupture. (A) Two-dimensionaland simultaneous color Doppler image of the parasternal long-axis (LAX) view with turbulent color Doppler flow across themembranous septum (yellow arrow). The continuous-waveDoppler signal (B) shows pancyclic, high-velocity flow.


population of patients with severe AS, a noncompliant aorta aswell as hypertrophied ventricle may preclude the use of standardmeasures of aortic regurgitant severity. For instance, large regurgi-tant volumes ($60 mL) may be seen in chronic severe AR with adilated ventricle, but for a small, hypertrophied ventricle, acutesevere AR may be defined as a much smaller regurgitant volume.Second, the atypical and irregular nature of the PAR jets may limitthe accuracy of qualitative, semiquantitative, and quantitative pa-rameters used for native or surgical valve disease and thus changethe approach and severity grading. Third, proprietary valvedesigns may require design-dependent imaging algorithms toassess PAR or valve function.

Other complications of TAVR have been extensively reviewed forboth the balloon-expandable and self-expanding valves.151,152

Importantly, intraprocedural TTE can also rule out the causes ofacute hemodynamic compromise listed in Table 12. Other complica-tions, such as perforations (Figure 12), occur rarely152 but can beeasily detected on 2D and Doppler imaging.

Postprocedural Assessment. A comprehensive evaluation ofchamber and valvular morphology and function should be per-formed after TAVR (Table 9). An accurate calculation of post-TAVR valve area requires a measurement of LVOT stroke vol-ume.181,182 Because of flow acceleration within the balloon-expandable stented valve,181 the LVOT diameter should bemeasured from the outer to outer stent frame with the pulsed-wave Doppler sample volume placed just apical to the proximaledge of the stent (Figure 13, Table 2). This diameter measurementhas been shown to correlate best with measurements of meangradient.182 Continuous-wave Doppler across the THV is performedto confirm gradients and calculate valve area. If the LVOT diametercannot be accurately measured, the Doppler velocity index is re-corded and may be a useful measurement for long-term follow-upof valve function. Recent reports of the PARTNER trial suggest

Figure 13 Measuring AVA following TAVR. Because of flow acceleration within the balloon-expandable stented valve, the LVOTdiameter should be measured from the outer to outer stent frame (A) with pulsed-wave Doppler sample volume placed just apicalto the proximal edge of the stent (B). Continuous-wave Doppler is then used to calculate AVA (C).


Hahn et al 23

that the Doppler velocity index in normal balloon-expandable valveshould be >0.45.146 If the stent protrudes into the LVOT cavity(failing to make contact with surrounding tissue), particularly ifflow is seen around the outside of inflow stent, then stroke volumemeasurements using this region of the THV may be invalid. The in-ner to inner stent diameter at the level of the prosthetic leaflet hingepoints can be used with the pulsed-wave Doppler at this same level,

but given the flow acceleration, this calculated valve area typicallyoverestimates the true area. Initial studies of the self-expanding valvesuggested that the LVOT diameter should be taken from the justbelow the hinge points of the visible prosthetic leaflets, measuringthe inner to inner stent.183 Recent trials, however, have used theouter to outer edge of the ventricular edge of the transcathetervalve.153


CONCLUSIONS

In 10 short years, TAVR has become standard of care for inoperable, anequivalent option for high-risk patients, and a consideration forintermediate-risk patients with severe symptomatic AS. Understandingthe anatomic variability and constraints of the THV for this procedureas well as the importance and value of echocardiographic imaging isimportant for anymember of theheart team taking care of thesepatients.

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